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"Ecstasy" to addiction: Mechanisms and reinforcing effects of three synthetic cathinone analogs of MDMA.
Neuropharmacology. 2018 05 01; 133:171-180.N

Abstract

This study aimed to address the mechanisms and reinforcing effects of three synthetic cathinone analogs of MDMA commonly reported in "Ecstasy" formulations: methylone, butylone, and pentylone. Whole-cell patch clamp techniques were used to assess the mechanism of each compound at the dopamine and serotonin transporters. Separate groups of rats were trained to discriminate methamphetamine, DOM, or MDMA from vehicle. Substitution studies were performed in each group and antagonism studies with SCH23390 were performed against each compound that produced substitution. Self-administration of each compound was evaluated under a progressive ratio schedule of reinforcement. Each compound produced an inward current at the serotonin transporter, but little or no current at the dopamine transporter. Each of the test compounds substituted fully for the discriminative stimulus effects of methamphetamine, methylone and butylone substituted partially for DOM and fully for MDMA, whereas pentylone failed to substitute for DOM and substituted only partially for MDMA. SCH23390 fully and dose-dependently attenuated methamphetamine-appropriate responding produced by each test compound, but was least potent against pentylone. MDMA-appropriate responding was minimally affected by SCH23390. Each test compound was robustly self-administered with pentylone producing the greatest self-administration at the doses tested. Given the prevalence of synthetic cathinones in "Ecstasy" formulations, these data indicate that adulterated "Ecstasy" formulations may drive more compulsive drug use than those containing only MDMA.

Authors+Show Affiliations

Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX, USA. Electronic address: Sean.dolan@live.unthsc.edu.Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX, USA. Electronic address: Zhenglan.chen@unthsc.edu.Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX, USA. Electronic address: Ren-qi.huang@unthsc.edu.Department of Pharmacology and Neuroscience, University of North Texas Health Science Center, 3500 Camp Bowie Blvd, Fort Worth, TX, USA. Electronic address: Michael.gatch@unthsc.edu.

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

29378213

Citation

Dolan, Sean B., et al. ""Ecstasy" to Addiction: Mechanisms and Reinforcing Effects of Three Synthetic Cathinone Analogs of MDMA." Neuropharmacology, vol. 133, 2018, pp. 171-180.
Dolan SB, Chen Z, Huang R, et al. "Ecstasy" to addiction: Mechanisms and reinforcing effects of three synthetic cathinone analogs of MDMA. Neuropharmacology. 2018;133:171-180.
Dolan, S. B., Chen, Z., Huang, R., & Gatch, M. B. (2018). "Ecstasy" to addiction: Mechanisms and reinforcing effects of three synthetic cathinone analogs of MDMA. Neuropharmacology, 133, 171-180. https://doi.org/10.1016/j.neuropharm.2018.01.020
Dolan SB, et al. "Ecstasy" to Addiction: Mechanisms and Reinforcing Effects of Three Synthetic Cathinone Analogs of MDMA. Neuropharmacology. 2018 05 1;133:171-180. PubMed PMID: 29378213.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - "Ecstasy" to addiction: Mechanisms and reinforcing effects of three synthetic cathinone analogs of MDMA. AU - Dolan,Sean B, AU - Chen,Zhenglan, AU - Huang,Renqi, AU - Gatch,Michael B, Y1 - 2018/01/31/ PY - 2017/09/11/received PY - 2017/12/14/revised PY - 2018/01/15/accepted PY - 2018/1/30/pubmed PY - 2018/11/14/medline PY - 2018/1/30/entrez KW - Drug discrimination KW - MDMA KW - Patch clamp KW - Self-administration KW - Synthetic cathinones SP - 171 EP - 180 JF - Neuropharmacology JO - Neuropharmacology VL - 133 N2 - This study aimed to address the mechanisms and reinforcing effects of three synthetic cathinone analogs of MDMA commonly reported in "Ecstasy" formulations: methylone, butylone, and pentylone. Whole-cell patch clamp techniques were used to assess the mechanism of each compound at the dopamine and serotonin transporters. Separate groups of rats were trained to discriminate methamphetamine, DOM, or MDMA from vehicle. Substitution studies were performed in each group and antagonism studies with SCH23390 were performed against each compound that produced substitution. Self-administration of each compound was evaluated under a progressive ratio schedule of reinforcement. Each compound produced an inward current at the serotonin transporter, but little or no current at the dopamine transporter. Each of the test compounds substituted fully for the discriminative stimulus effects of methamphetamine, methylone and butylone substituted partially for DOM and fully for MDMA, whereas pentylone failed to substitute for DOM and substituted only partially for MDMA. SCH23390 fully and dose-dependently attenuated methamphetamine-appropriate responding produced by each test compound, but was least potent against pentylone. MDMA-appropriate responding was minimally affected by SCH23390. Each test compound was robustly self-administered with pentylone producing the greatest self-administration at the doses tested. Given the prevalence of synthetic cathinones in "Ecstasy" formulations, these data indicate that adulterated "Ecstasy" formulations may drive more compulsive drug use than those containing only MDMA. SN - 1873-7064 UR - https://www.unboundmedicine.com/medline/citation/29378213/"Ecstasy"_to_addiction:_Mechanisms_and_reinforcing_effects_of_three_synthetic_cathinone_analogs_of_MDMA_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0028-3908(18)30020-0 DB - PRIME DP - Unbound Medicine ER -